The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies
Abstract
:1. General Introduction: Development, the Maternal Immune System, and Immune Tolerance
1.1. Development and Trophoblast Invasion
1.2. Interaction Sites and the Concept of Maternal-Fetal Immune Tolerance
1.3. The Immune System at the Maternal-Fetal Interface
1.4. Immune Evasion of Trophoblasts
2. The General Outlook of Macrophages in Pregnancy
3. View on Macrophages at Early Pregnancy
3.1. Immune Cell Frequencies
3.2. Spiral Artery Remodeling
3.3. Macrophage Subtypes and Interaction with Trophoblasts
4. View on Macrophages during Late Pregnancy
4.1. Immune Regulatory Molecules
4.2. HLA-DR and Cell-Cell Interactions
4.3. HLA Incompatibility, Immune Parameters and Pregnancy Outcomes
5. Macrophages in Complicated Pregnancies
5.1. Women with Unexplained Recurrent Pregnancy Loss
5.2. Miscarriage Related to Chronic Histiocytic Intervillositis
5.3. Insight on Macrophage Subsets in uRPL from Single-Cell Studies
6. Summary
Author Contributions
Funding
Conflicts of Interest
References
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Gestation | Main Subtypes | Resident Marker | Other Markers | Possible Function | Reference |
---|---|---|---|---|---|
6–8 week | CD11chiCCR2+ (14%) | TNF pathway; IL1-β; COX2 | phagocytosis; inflammatory-related | [59] | |
CD11chiCRR2− (6%) | HMOX1 | anti-inflammatory; anti-oxidative | |||
CD11cloCCR2− (80%) | CD209hi | DC-SIGNhi; HLA-DRhi | |||
6–12 week | CD11chi (20%) | CD206lo; CD209lo | HLA-DR; TNFα; IL-6, IL10 | inflammatory processes; lipid metabolism | [58] |
CD11clo (69%) | CD206hi; CD209hi | HLA-DR; TGFβ | ECM formation; growth regulation | ||
6–12 week | CD11chi | IL-10hi; TNF, IL-1, IL-6, VEGF-A | remodeling | [60] | |
CD11clo | CCL-2, CCL-8, IGF-1, HGF, PDGF | self-renewal; remodeling | |||
10–11 week | DC-SIGN/CD209+ | CD163+; CD204+ | M1 (28%): CD11blo; CD11c−; HLA-DR− | close to trophoblasts | [43] |
M2 (4%): CD11b+; CD11c−; HLA-DR+ | |||||
M3 (8%): CD11blo; CD11clo; HLA-DR+ | |||||
DC-SIGN/CD209− | CD163+; CD204+ | M4 (52%): CD11b−; CD11c−; HLA-DR− | close to trophoblasts | ||
M5 (5%): CD11blo; CD11c−; HLA-DR+ | |||||
6–20 week | DC-SIGN/CD209+ | CD163+; CD206+ | M2a (64%): CD11c−; HLA-DR+ | upregulate TIM-3 and GAL-9 with increased GA | [40] |
M2b (2.7%): CD11c+; HLA-DR+ | upregulate TIM-3 and GAL-9 with increased GA | ||||
M2c (10.3%): CD11c−; HLA-DR− | |||||
DC-SIGN/CD209− | CD163+; CD206+ | M1a (19%): CD11c−; HLA-DR+ | |||
M1b (4%): CD11c−; HLA-DR+ |
Studied Cell Types | Main Findings | Reference |
---|---|---|
M1 macrophages: CD68+IL-10lowiNOS+ M2 macrophages: CD68+IL10+iNOSlow | M1 numbers decrease in healthy pregnancy, but stay the same in uRPL during first trimester M2 numbers increase in healthy pregnancy, but decrease in uRPL during first trimester | [92] |
CCR1+ macrophages: CD163+CD206+ IL-10+ TGF-β+ CD80low CD86low | CCR1+ macrophages enriched in healthy 1st trimester decidua, but not in uRPL CCR1+ macrophages during uRPL have an attenuated immunosuppressive phenotype | [94] |
Mac1: M1 polarization characteristics Mac2: enriched with M2 specific genes | Mac1 proportion modestly elevated and mac2 proportion highly decreased in uRPL Mac2 interacts with NK cells during healthy pregnancy, but switches toward interaction with T cells in uRPL | [41] |
10 CD14+ monocyte/macrophages clus-ters | cluster 6 macrophages with both M1- (CD163, IL-10) and M2-features (CCL2,-3,-4) enriched in uRPL | [61] |
M1: CD68+CD11b+CD206lowCD11c+ M2: CD68+CD11bmedCD206+CD11cmed | M1 proportion two-fold higher and M2 proportion slightly decreased in uRPL CD11chighCCR2− macrophage proportions increased and CD11clowCCR2− macrophages decreased in uRPL | [42] |
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Krop, J.; Tian, X.; van der Hoorn, M.-L.; Eikmans, M. The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies. Int. J. Mol. Sci. 2023, 24, 5300. https://doi.org/10.3390/ijms24065300
Krop J, Tian X, van der Hoorn M-L, Eikmans M. The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies. International Journal of Molecular Sciences. 2023; 24(6):5300. https://doi.org/10.3390/ijms24065300
Chicago/Turabian StyleKrop, Juliette, Xuezi Tian, Marie-Louise van der Hoorn, and Michael Eikmans. 2023. "The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies" International Journal of Molecular Sciences 24, no. 6: 5300. https://doi.org/10.3390/ijms24065300